Induction and transmission of oncogene-induced senescence
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Cellular and Molecular Life Sciences
REVIEW
Induction and transmission of oncogene‑induced senescence Nattaphong Rattanavirotkul1 · Kristina Kirschner2 · Tamir Chandra3 Received: 1 February 2020 / Revised: 27 July 2020 / Accepted: 3 September 2020 © The Author(s) 2020
Abstract Senescence is a cellular stress response triggered by diverse stressors, including oncogene activation, where it serves as a bona-fide tumour suppressor mechanism. Senescence can be transmitted to neighbouring cells, known as paracrine secondary senescence. Secondary senescence was initially described as a paracrine mechanism, but recent evidence suggests a more complex scenario involving juxtacrine communication between cells. In addition, single-cell studies described differences between primary and secondary senescent end-points, which have thus far not been considered functionally distinct. Here we discuss emerging concepts in senescence transmission and heterogeneity in primary and secondary senescence on a cellular and organ level. Keywords Oncogene-induced senescence · Secondary senescence · Notch signalling · Juxtacrine senescence
Introduction Cellular senescence is a stress response programme that irreversibly and stably arrests the cell cycle following a variety of intrinsic and extrinsic stressors such as shortening of the chromosomal termini, DNA damage, oxidative stress, oncogenic and mitogenic stimuli [1–3]. Cellular senescence was first described by Hayflick and Moorhead, who observed that cultured human fibroblasts undergo a finite number of cell divisions, a phenomenon later widely known as the ‘Hayflick limit’ and termed as replicative senescence [4]. The limited replicative capacity of cells in vitro spontaneously suggests a model for ageing at the cellular level. It is now clear that * Nattaphong Rattanavirotkul [email protected] * Kristina Kirschner [email protected] * Tamir Chandra [email protected] 1
Chakri Naruebodindra Medical Institute, Ramathibodi Medical School, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 111, Bang Pla, Bang Phli, Samut Prakan 10540, Thailand
2
Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UK
3
MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK
this proliferative arrest is mainly driven by telomere attrition [5]. Initially dismissed as an in vitro artefact that bore no relevance to biological mechanisms in vivo, the concept of cellular senescence has stood the test of the past five decades and evolved to become relevant beyond the ageing context, with critical physiological functions in preventing tumour formation, remodelling of tissues during embryonic development, and promoting wound healing and immunogenic clearance [6]. In the replicative senescence model of proliferating human cells, successive telomere erosion in each cell division ultimately uncaps the free double-stranded chromosome ends, causing them to be recognised as DNA d
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